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Contains fulltext : 282870.pdf (Publisher’s version ) (Open Access) BACKGROUND: Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data specifically on this growing population are available, e.g. regarding the safety and performance of biological treatment. AIMS: We aimed to give insight into this specific population by comparing the drug survival and safety of biologics in older patients with that in younger patients. METHODS: In this real-world observational study, data from 3 academic and 15 non-academic centers in The Netherlands were extracted from the prospective BioCAPTURE registry. Biologics included in this study were tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors. Patients were divided into two age groups: ≥ 65 years and

The coronavirus disease 2019 (COVID-19) pandemic is caused by rapid spread of different strains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity of infection ranges from mild, or even asymptomatic, to very severe. Signs and symptoms include fatigue, fever, exanthemas, upper respiratory illness, loss of smell and taste, pneumonia, severe acute respiratory syndrome, and multi-organ failure. Risk factors for a severe or lethal course include age, male gender, obesity, diabetes, cardiovascular disease, and immune suppression1 .

Background Janus kinase (JAK) inhibition is a new mode of action in atopic dermatitis (AD); clarity about drug class safety considerations in the context of AD is important. Baricitinib, an oral, reversible, selective inhibitor of JAK1/JAK2, is in late-stage development for adult patients with moderate-to-severe AD. Objective To report pooled safety data for baricitinib in patients with moderate-to-severe AD in the clinical development program including long-term extension (LTE) studies. Methods This analysis included patient-level safety data from six double-blinded, randomized, placebo-controlled studies (one phase 2 and five phase 3), one double-blinded, randomized, LTE study and one open-label LTE study, reported in three data sets: placebo-controlled, 2-mg - 4-mg extended and All-bari AD. Safety outcomes include treatment-emergent adverse events, adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates were calculated. Results Data were collected for 2531 patients who were given baricitinib for 2247 patient-years (median duration 310 days). The frequency of serious infections, opportunistic infections and conjunctival disorders was low and similar between treatment groups in the placebo-controlled period. The most common serious infections were eczema herpeticum [n = 11, incidence rates (IR) = 0.5], cellulitis (n = 6, IR = 0.3) and pneumonia (n = 3, IR = 0.1). There were four opportunistic infections (IR = 0.2). No malignancies, gastrointestinal perforations, positively adjudicated cardiovascular events or tuberculosis were reported in the placebo-controlled period in baricitinib-treated patients. Frequency of herpes simplex was higher in the 4-mg group (6.1%) vs. the 2-mg (3.6%) and placebo group (2.7%); IRs in the extended data set (2-mg IR = 9.6; 4-mg IR = 14.5) were lower vs. the placebo-controlled data set (2-mg IR = 12.4; 4-mg IR = 21.3). In the All-bari AD data set, there were two positively adjudicated major adverse cardiovascular events (2-mg group): two venous thrombosis events (4-mg group) and one death. Conclusion This integrated safety analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib.

Author(s): Thyssen, JP; de Bruin-Weller, MS; Paller, AS; Leshem, YA; Vestergaard, C; Deleuran, M; Drucker, AM; Foelster-Holst, R; Traidl-Hoffmann, C; Eyerich, K; Taieb, A; Su, JC; Bieber, T; Cork, MJ; Eichenfield, LF; Guttman-Yassky, E; Wollenberg, A | Abstract: BackgroundConjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab.ObjectiveTo survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC).MethodsElectronic survey and in-person discussion of management strategies.ResultsForty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist.LimitationsThe study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey.ConclusionThe IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

Summary Background Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. Objectives To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. Methods We evaluated randomized placebo‐controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). Results In most AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. Conclusions Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab‐treated patients require further study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD).In most dupilumab AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than those receiving placebo.Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare.Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add? This analysis confirms and extends the results of the individual clinical trials.Baseline disease‐related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation‐regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis.Patients who responded well to dupilumab had reduced incidence of conjunctivitis.Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab‐treated patients with AD., Linked Editorial: https://doi.org/10.1111/bjd.18255. https://doi.org/10.1111/bjd.18276 available online https://www.bjdonline.com/article/

Since the introduction of active vaccination against SARS-CoV-2 infection, there has been a debate about the risk of developing severe allergic or anaphylactic reactions among individuals with a history of allergy. Indeed, rare cases of severe allergic reactions have been reported in the United Kingdom and North America. By february 2021 a rate of 4,5 severe allergic reactions occurred among 1 million patients vaccinated with the mRNA-based COVID-19 vaccines, which is higher than the generally expected rate of severe allergic reactions to vaccinations of around 1 in 1 million.

International audience; Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier-stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti-inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid-potency corticosteroids are proven agents for proactive therapy, which is defined as the long-term intermittent anti-inflammatory therapy of frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit-risk ratio. The IL-4R-blocker dupilu-mab is a safe, effective and licensed, but expensive, treatment option with potential ocular side-effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) only have limited effects on AD-related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient-specific, and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. Efficacy-proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults.

Atopic dermatitis (AD) is a complex disease with elevated risk of respiratory comorbidities.1,2 Severely affected patients are often treated with immune-modulating systemic drugs.3,4 On March 11th 2020, the World Health Organization declared the 2019 novel coronavirus severe acute respiratory syndrome (SARS-Cov-2) epidemic to be a pandemic. The number of cases worldwide is increasing exponentially and poses a major health threat, especially for those who are elderly, immuno-compromised, or have comorbidities. This also applies to AD patients on systemic immune-modulating treatment. In these days of uncertainty, reallocation of medical resources, curfew, hoarding, and shutdown of normal social life, patients, caregivers and doctors ask questions regarding the continuation of systemic immune-modulating treatment of AD patients. The ETFAD decided to address some of these questions here.

Summary Background Guidelines discourage the use of systemic corticosteroids for atopic dermatitis (AD), but their use remains widespread. Objectives To reach consensus among an international group of AD experts on the use of systemic corticosteroids for AD. Methods A survey consisting of statements accompanied by visual analogue scales ranging from ‘strongly disagree’ to ‘neutral’ to ‘strongly agree’ was distributed to the International Eczema Council (IEC). Consensus was reached in agreement on a statement if, What's already known about this topic? Despite recommendations against their use in practice guidelines, systemic corticosteroids are commonly used for atopic dermatitis (AD). What does this study add? The International Eczema Council reached consensus on circumstances in which systemic corticosteroids can be used for AD, including a lack of other treatment options, as a bridge to other systemic therapies or phototherapy, during acute flares in need of immediate relief, in anticipation of a major life event, or in the most severe cases.Clinicians should limit the use of systemic corticosteroids for severe AD to those circumstances. https://doi.org/10.1111/bjd.16385 available online https://goo.gl/Uqv3dl

Azathioprine is frequently used in severe eczema. It is converted in the liver into active metabolites, including 6-thioguanine nucleotide (6-TGN) and methylated 6-methylmercaptopurine (6-MMP). In the past, the therapeutic potential of azathioprine may have not been fully utilized. Recent investigations on inflammatory bowel disease have led to a better understanding of azathioprine metabolism and optimizing treatment.To investigate whether measuring thiopurine metabolites in circulation can improve the effectiveness and safety of azathioprine treatment in patients with atopic dermatitis and/or chronic hand/foot eczema.Azathioprine metabolite levels were measured in eczema patients during maintenance treatment (Part I) and dose escalation (Part II). Clinical effectiveness, hepatotoxicity, and bone marrow suppression were analyzed and TPMT genotype was assessed.A wide variation in metabolite levels in all dose groups was observed. In Part I (32 patients), there were no significant differences in 6-TGN levels between clinical responders and non-responders (p = .806). No hepatoxicity or myelotoxicity was observed. In Part II, all 6-TGN and 6-MMP levels increased during dose escalation. Hypermethylation was observed in 2/8 patients.For individual eczema patients treated with azathioprine, routinely measuring 6-TGN and 6-MMP can be helpful in optimizing azathioprine dose, improving clinical effectiveness, and preventing side effects.

BACKGROUND: Oral immunosuppressive drugs are frequently prescribed in young women with atopic dermatitis (AD). Immunocompromised patients may have a higher risk of developing high risk HPV infections, CIN and cervical carcinoma. Most literature on patients using oral immunosuppressive drugs is available in organ transplant patients. Literature on the risk of developing cervical carcinoma in AD patients treated with oral immunosuppressive drugs is lacking. At this moment there is no clear guideline/consensus on this topic, but in daily practice, questions arise concerning whether this risk is increased and whether more intensive screening in women using immunosuppressive drugs should take place.OBJECTIVE: To investigate the occurrence of cervical carcinoma in women with AD treated with oral immunosuppressive drugs.METHODS: In this retrospective cohort study in two university medical centers in the Netherlands, all female adult AD patients receiving oral immunosuppressive drugs (cyclosporine A, azathioprine, methotrexate, mycophenolate mofetil, enter-coated mycophenolic acid and extended release tacrolimus) for more than 2 months between 1989 and January 1(st) 2014 were included. Patient files in the national histopathology register were screened for PAP3a, CIN I, CIN II, CIN III and cervical carcinoma.RESULTS: A total of 257 female AD patients with one or more treatment episodes from 1989 until January 1(st) 2014 were identified and included in this study. In 189 patients (73.5%) results of cervical examination were reported in the national histopathology database. Median total duration of treatment in these 189 women was 407.0 days (IQR 243.0-940.0). No cervical carcinoma during or following immunosuppressive therapy was found in our patient group.CONCLUSIONS: No intensified screenings program for cervical neoplasia seems necessary for women with AD using oral immunosuppressive drugs. This article is protected by copyright. All rights reserved.

Summary Background For many years dermatologists have had access to few therapies for patients with moderate‐to‐severe atopic eczema (AE). New promising therapies are entering the market but conventional phototherapies and systemic therapies have more well‐known safety profiles, lower costs and wider availability. Objectives To provide insight into current prescribing practices of conventional phototherapy and systemic immunomodulatory therapies for adults with chronic AE, and the factors influencing these prescribing practices, before biologics and other novel therapeutics become routine clinical practice. Methods In this exploratory study dermatologists were invited to participate in an online survey via a mailing list of the European Academy of Dermatology and Venereology and national societies. Data were collected on participant characteristics (including clinical practice data), the use of phototherapies and systemic therapies, and factors influencing their use. Results From 30 European countries, 238 out of 361 dermatologists willing to participate (65·9%) completed the survey, with 229 meeting the inclusion criteria. For phototherapy (prescribed by 84·7%), most preferred narrowband ultraviolet B as first line (80·9%) and psoralen plus ultraviolet A as second (21·6%). For systemic therapy (prescribed by 95·2%) ciclosporin (54·1%), oral corticosteroids (32·6%) and methotrexate (30·7%) were used first line. Dermatologists relied mostly on personal experience for prescribing phototherapy and systemic therapy. Azathioprine and mycophenolic acid were prescribed by only 135 (59·0%) and 85 (37·1%) participants in total, mostly due to a lack of personal experience. Conclusions This study provides insight into prescribing practices for conventional phototherapy and systemic therapy in Europe and shows that off‐label therapies are also preferred as first‐line choice of systemic therapy., What is already known about this topic? Varying prescribing practices were found for adult (in the UK) and paediatric (in Northern America and Europe) patients with moderate‐to-severe atopic eczema (AE).Not much is known about the prescription of phototherapy and (off‐label) systemic therapy for adult patients in Europe.Although therapies like dupilumab are promising new treatment modalities, better‐known safety profiles, lower costs and better availability are reasons to improve the evidence profile of conventional systemic therapies like ciclosporin. What does this study add? Prescribing practices of European dermatologists treating adult patients with moderate‐to-severe AE show diversity.Most dermatologists prefer narrowband ultraviolet B as first‐line phototherapy, followed by psoralen plus ultraviolet A as second line.Next to ciclosporin, which is most commonly prescribed, (off‐label) methotrexate and oral corticosteroids are also frequently used as first‐line systemic agents in chronic AE.Lack of personal experience with azathioprine and mycophenolic acid was the most important reason against their prescription. What are the clinical implications of the work? The results from this study might help to improve the experience with, and prescribing of, all available conventional phototherapies and (off‐label) systemic therapies.Guidelines developers might use these results to develop and implement treatment algorithms. Linked Comment: Bruin‐Weller. Br J Dermatol 2020; 183:987–988. Plain language summary available online

International audience; Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine.

Results from clinical studies indicate that azathioprine and enteric-coated mycophenolate sodium (EC-MPS) are safe and potent drugs in the treatment of atopic dermatitis (AD).(1-5) However, published data from large groups of non-selected patients is non-existent to date which hampers generalization to daily practice. In addition, head-to-head trials in which azathioprine and EC-MPS are compared, have never been performed. The primary objective was to perform an analysis of drug survival for azathioprine and EC-MPS in a long-term daily practice cohort of patients with AD. The secondary objective was to identify determinants of drug survival. This article is protected by copyright. All rights reserved.

BackgroundThere are gaps in our knowledge of the prevalence of adult atopic dermatitis (AD). ObjectiveTo estimate the prevalence of AD in adults and by disease severity. MethodsThis international, cross-sectional, web-based survey was performed in the United States, Canada, France, Germany, Italy, Spain, United Kingdom, and Japan. Adult members of online respondent panels were sent a questionnaire for AD identification and severity assessment; demographic quotas ensured population representativeness for each country. A diagnosis of AD required subjects to be positive on the modified UK Working Party/ISAAC criteria and self-report of ever having an AD diagnosis by a physician. The proportion of subjects with AD who reported being treated for their condition was determined and also used to estimate prevalence. Severity scales were Patient-Oriented SCORAD, Patient-Orientated Eczema Measure, and Patient Global Assessment. ResultsAmong participants by region, the point prevalence of adult AD in the overall/treated populations was 4.9%/3.9% in the US, 3.5%/2.6% in Canada, 4.4%/3.5% in the EU, and 2.1%/1.5% in Japan. The prevalence was generally lower for males vs females, and decreased with age. Regional variability was observed within countries. Severity varied by scale and region; however, regardless of the scale or region, proportion of subjects reporting severe disease was lower than mild or moderate disease. ConclusionsPrevalence of adult AD ranged from 2.1% to 4.9% across countries. Severe AD represented a small proportion of the overall AD population regardless of measure or region.

Introduction Le dupilumab (DPL), un anticorps monoclonal entierement humain, bloquant la composante commune des recepteurs des interleukines IL-4 et IL-13, est approuve aux USA pour les patients (pts) de 12 ans et plus atteints de dermatite atopique (DA) moderee a severe insuffisamment controlee par des traitements topiques soumis a prescription ou chez qui ces traitements sont deconseilles ; au Japon pour les pts adultes atteints de DA insuffisamment controlee par les traitements existants et en Europe pour les pts de 18 ans et plus atteints de DA moderee a severe candidats a un traitement systemique. Dans cette etude, nous analysons l’effet du DPL (vs placebo, PBO) chez des pts recrutes dans l’etude de phase 3 LIBERTY AD CAFE ( NCT02755649 ) ayant precedemment utilise un immunosuppresseur systemique. Materiel et methodes CAFE etait une etude de phase 3, multinationale, multicentrique, en double aveugle chez des adultes avec DA moderee a severe et des antecedents de reponse insuffisante ou d’intolerance a la ciclosporine A. Ces adultes (n = 325) ont ete randomises (1 : 1 : 1) pour recevoir, pendant 16 semaines, 300 mg de DPL par voie sous-cutanee en association avec des dermocorticoides (DC) soit une fois par semaine, chaque semaine (1×/s + DC), soit une fois toutes les 2 semaines (1×/2 s + DC) ou PBO + DC. Nous presentons la proportion de pts ayant presente une amelioration de 75 %/50 % de leur valeur initiale du score Eczema Area and Severity Index (EASI, indice de surface et de severite de l’eczema) (EASI-75/EASI-50) et les donnees sur la securite. Resultats Deux cent vingtsept pts ont recu un traitement anterieur par des Is (PBO + DC n = 73, 1×/2 s + DC n = 76, 1×/s + DC n = 78) ; 210 pts ont recu de la ciclosporine, 30 du methotrexate, 26 de l’azathioprine et 16 du mycophenalate mofetil. Plus de pts recevant du DPL sont parvenus a un EASI-75 a la semaine 8 vs PBO + DC (21,9 % PBO + DC, 50,0 % 1×/2 s + DC ; p = 0,0005 vs PBO + DC, 51,3 % 1×/s + DC ; p = 0,0002 vs PBO + DC), en augmentation a la semaine 16 (26,0 % PBO + DC, 59,2 % 1×/2 s + DC, 57,7 % 1×/s + DC ; p Conclusion Dans l’etude CAFE, plus de 70 % des pts sous DPL precedemment traites par des Is sont parvenus a un EASI-50 a la semaine 8 et plus de 80 % a la semaine 16. Ces resultats demontrent que le DPL est efficace chez cette population de pts plus gravement atteints, avec une securite acceptable.

Introduction Le dupilumab (DPL) est approuve dans plusieurs pays pour le traitement des patients (pts) adultes souffrant de dermatite atopique (DA) moderee a severe insuffisamment controlee. Materiel et methodes Il s’agit d’une analyse post-hoc des donnees groupees de deux essais de phase 3 (SOLO1 : NCT02277743 ; SOLO2 : NCT02277769 ) visant a determiner si des pts adultes atteints de DA moderee a severe traites par le DPL et non parvenus a un score d’evaluation globale par l’investigateur (IGA) de 0/1 a la 16e semaine (s) presentaient une amelioration cliniquement significative pour un ou plusieurs des trois domaines majeurs de la DA (signes, symptomes et qualite de vie [QdV]). Les pts ont ete randomises selon un rapport 1/1/1 pour recevoir pendant 16 s 300 mg de DPL par voie SC une fois par S (1×/s), toutes les 2 s (1×/2 s) ou un placebo (PBO). Les reponses cliniquement significatives etaient definies sur un ou plusieurs des criteres suivants : reduction ≥ 50 % du score EASI (indice de surface et de severite de l’eczema) (EASI-50), amelioration ≥ 3 points de la moyenne hebdomadaire du score NRS de prurit, amelioration ≥ 4 points du score DLQI (indice de qualite de vie dermatologique) ou amelioration ≥ 4 points du POEM (mesure de l’eczema par le patient) par rapport a l’initiation. Les criteres d’evaluation ont ete evalues apres 1, 2, 4, 8, 12 et 16 s. Resultats Au total, 1379 pts ont ete randomises : 460 pour PBO, 457 pour DPL 300 mg 1×/2 s et 462 pour DPL 300 mg 1×/s. Dans les groupes PBO/1×/2 s/1×/s, 417/288/292 pts respectivement ne sont pas parvenus a un IGA de 0/1 a la s16. Parmi ceux-ci, une proportion significativement plus importante de pts des deux groupes de traitement DPL vs PBO etait parvenue a un resultat cliniquement significatif pour une ou plusieurs des quatre mesures de severite de la DA/QdV apres seulement S1 (1×/s/1×/2 s vs PBO : 60,6 %/60,4 % vs 38,4 % ; p Fig. A ). Lorsque l’on analyse les scores de severite de la DA/QdV entre les s2 et s16, une proportion significativement plus importante de pts des groupes 1×/s/1×/2 s vs PBO sont parvenus a une reponse cliniquement significative pour chacune des mesures de severite de la DA/QdV. Les evenements indesirables plus frequents avec le DPL qu’avec le PBO etaient des reactions au site d’injection (1×/s/1×/2 s vs PBO : 15,82 %/10,97 % vs 6,14 %) et une conjonctivite (1×/s/1×/2 s vs PBO : 7,3 %/9,7 % vs 2,2 %). Conclusion Des pts adultes atteints de DA moderee a severe traites par le DPL et non parvenus a un IGA 0/1 a s16 ont presente une amelioration cliniquement significative rapide et persistante dans un ou plusieurs des principaux domaines de la DA (signes, symptomes et QdV) compare au PBO apres seulement s1 et jusqu’a s16.

Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93–80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage.

Introduction Le dupilumab, un anticorps monoclonal anti-IL-4R alpha entierement humain derive du VelocImmune, inhibe la signalisation de l’IL-4 et de l’IL-13, les principales responsables de l’inflammation de type 2 dans la dermatite atopique (DA). Le dupilumab est approuve aux Etats-Unis chez les patients âges de 12 ans et plus atteints de DA moderee a severe insuffisamment controlee par des traitements topiques ou chez qui ces traitements sont deconseilles ; au Japon pour les patients adultes atteints de DA insuffisamment controlee par les traitements existants, et en Europe pour les patients adultes atteints de DA moderee a severe qui necessitent un traitement systemique. Le SCORing AD (SCORAD) est un score de severite de la DA valide qui comprend l’etendue (partie A), l’intensite des signes (partie B) et les symptomes (partie C, evaluant le prurit et le sommeil) qui est employe pour mesurer la severite globale de la maladie d’apres les recommandations europeennes sur la DA. Dans cet abstract, nous decrivons les effets a long terme de l’association de dupilumab avec des dermocorticoides (DC) sur les resultats du SCORAD chez des patients atteints de DA moderee a severe ( NCT02260986 ). Materiel et methodes Les patients ont recu par voie sous-cutanee 300 mg de dupilumab associe a des DC soit une fois par semaine (1×/s + DC), soit toutes les 2 semaines (1×/2s + DC) ou un placebo 1×/s associe a des DC (PBO + DC) pendant 52 semaines. Les resultats comprenaient la modification moyenne du SCORAD (moindres carres [MC] en valeur absolue et %) entre le debut de l’etude et la 52e semaine, la proportion de patients presentant une amelioration ≥ 50 % du SCORAD (SCORAD-50) et l’evolution de chacune des composantes du SCORAD sur cette periode. Resultats Les caracteristiques au debut de l’etude etaient generalement similaires pour tous les groupes de traitement. L’association dupilumab + DC a induit une amelioration significative du SCORAD (en valeur absolue et en %) entre le debut de l’etude et la 52e semaine par rapport a l’association PBO + DC. Une plus grande proportion de patients atteignant un SCORAD-50 et une amelioration persistante, statistiquement et cliniquement significative, telle que mesuree par les composantes A, B et C du SCORAD, ont ete observees apres le traitement par le dupilumab par rapport l’association PBO + DC. Le dupilumab presentait un profil de securite acceptable. Conclusion L’association dupilumab + DC a ameliore significativement les valeurs du SCORAD par rapport a l’association PBO + DC sur 52 semaines. Des ameliorations ont ete observees pour chacune des trois composantes individuelles de l’echelle SCORAD : etendue de la maladie, intensite de signes et symptomes (prurit et sommeil).

Background: Although total IgE levels have been proposed as a biomarker for disease severity in atopic dermatitis (AD) and are increased in the majority of AD patients, they do not correlate with disease severity during short-term follow-up. During the synthesis of immunoglobulins, free light chains (Ig-FLCs) are produced in excess over heavy chains. In comparison with IgE molecules, Ig-FLCs have a very short serum half-life. Therefore, Ig-FLCs might be more suitable as a biomarker for disease severity during follow-up. Recent studies showed increased serum levels of kappa Ig-FLCs in infants with AD, correlating with disease severity. The aim of this study was to investigate serum kappa Ig-FLC levels in adults with AD, and their correlation to disease severity. Methods: Serum kappa If-FLC and total IgE levels were measured in 82 moderate to severe AD patients and 49 non-atopic controls. Blood was collected from patients before start of treatment with potent topical steroids (European classification: III-IV). 32 patients were treated during a clinical admission, and in this subpopulation a second blood sample was taken after 2 weeks of treatment. Clinical severity was determined by the Six Area Six Sign Atopic Dermatitis (SASSAD) severity score and a panel of serum biomarkers, including thymus and activation-regulated chemokine (TARC). Results: Serum kappa Ig-FLCs levels in adult AD patients were not increased compared to non-atopic controls. Moreover, we observed no correlation between kappa Ig-FLC serum levels and disease severity determined by SASSAD and a panel of serum biomarkers, including TARC. Serum kappa Ig-FLC levels did also not decrease during treatment. Conclusion: There are no differences in serum kappa Ig-FLC levels between adult patients suffering from moderate to severe AD compared to non-atopic controls. Moreover, serum levels of kappa Ig-FLCs cannot be used as a biomarker for disease severity in adult AD.

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Background Hand eczema is a common condition; it is often chronic and can be difficult to treat. Cyclosporine is used off-label to treat severe hand eczema; however, the evidence for this treatment is scarce.Objective To examine the drug survival of cyclosporine in a daily practice cohort of patients with chronic hand eczema.Methods This retrospective daily use study included hand eczema patients who were treated with cyclosporine between 01-06-1999 and 01-06-2014 in two Dutch university hospitals. Patient and treatment characteristics were retrospectively collected from medical charts. First treatment episodes were analysed by means of Kaplan-Meier drug survival curves. Possible determinants of drug survival were analysed by Cox regression models. Treatment effectiveness was analysed with a retrospective physician's global assessment.Results A total of 102 patients were treated with cyclosporine. The median drug survival rate was 0.86 years (10.3 months). The overall drug survival rate after 6 months, 1, 2 and 3 years were 61.7%, 45.2%, 18.6% and 13.9% respectively. Main reasons for discontinuation were adverse events, especially early in treatment, and ineffectiveness. After 3 months, a good response to treatment was recorded in 62.9% of the patients.Conclusion Cyclosporine had a median drug survival of 10.3 months. Especially patients with recurrent vesicular hand eczema showed a good treatment response.

Summary Background The Dermatology Department of the University Medical Centre Utrecht, the Netherlands, developed an e-health portal for patients with atopic dermatitis (AD), consisting of e-consultation, a patient-tailored website, monitoring and self-management training. Objectives To determine the cost-effectiveness of individualized e-health compared with usual face-to-face care for children and adults with AD. Methods A randomized controlled cost-effectiveness study from a societal perspective in adults and parents of children with moderate AD. Outcomes were quality of life, severity of AD, itching and direct and indirect costs. Data were collected at baseline and at 3 and 12 months after randomization. Linear mixed models were used to analyse clinical outcomes. After multiple imputation of missing data, costs and differences in costs were calculated over a period of 1 year. Results In total, 199 patients were included. There were no significant differences in disease-specific quality of life, severity of AD and intensity of itching between both groups at the three time points. The difference in direct costs between the intervention and control groups was €24 [95% confidence interval (CI) −360 to 383], whereas this difference was −€618 (95% CI −2502 to 1143) for indirect costs. Overall, individual e-health was expected to save €594 (95% CI −2545 to 1227) per patient in the first year of treatment, mainly through a reduction in work absenteeism. Uncertainty analyses revealed that the probability of e-health reducing costs was estimated to be ≥ 73%. Conclusions E-health during follow-up of patients with AD is, after initial diagnosis and treatment during face-to-face contact, just as effective as usual face-to-face care with regard to quality of life and severity of disease. However, when costs are considered, e-health is likely to result in substantial cost savings. Therefore, e-health is a valuable service for patients with AD.

Background Studies assessing the relationship between disease activity and quality of life (QoL) in adults with atopic dermatitis (AD), before and after therapy are lacking. The relation between disease activity and QoL in AD patients was evaluated before (t = 0) and after 6 weeks (t = 6) of treatment with cyclosporin 5 mg/kg. Methods In 54 patients with severe AD, disease activity was assessed using objective Scoring Atopic Dermatitis index (SCORAD), Six Area Six Sign Atopic Dermatitis (SASSAD), ‘rule of nines’ extent score and serum levels of thymus and activation-regulated chemokine (TARC). Patients filled out the Dermatology Life Quality Index (DLQI). To study the relation between disease activity and QoL, correlations were calculated and regression analysis was performed. Results At t = 0 there was a small, non-significant correlation between the DLQI and the objective SCORAD, ‘rule of nines’ or serum TARC levels. At t = 6 the objective SCORAD, serum TARC and the ‘rule of nines’ score showed moderate and significant correlations with the DLQI (r = 0.34, P = 0.02; r = 0.31, P = 0.03; r = 0.49, P

Atopic dermatitis is a chronic inflammatory skin disease that may require systemic therapy. Ciclosporin A (CsA) is a widely used, potent immunosuppressant but it is not effective in all patients with atopic dermatitis, and side-effects limit its use. Dupilumab, a fully human anti-interleukin 4 receptor-alpha monoclonal antibody, inhibits signaling of IL-4 and IL-13, key drivers of Type 2/Th2-mediated inflammation, and is approved in the U.S.A. and the European Union for the treatment of inadequately-controlled moderate-to-severe atopic dermatitis in adults.To evaluate efficacy and safety of dupilumab with concomitant topical corticosteroids (TCS) in adults with atopic dermatitis with inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable.In this 16-week, double-blind, randomized, placebo-controlled, phase III trial, patients were randomized 1 : 1 : 1 to subcutaneous dupilumab 300 mg weekly (qw) or every 2 weeks (q2w) or placebo. All received concomitant medium-potency TCS from Week -2 through Week 16; dosage could be tapered if lesions cleared, or stopped for adverse reactions to TCS.In total, 390 patients were screened, 325 were randomized, and 318 completed the trial. Treatment groups had similar baseline characteristics. Significantly more patients in the dupilumab qw + TCS and q2w + TCS groups achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index at Week 16 vs. the placebo + TCS group (primary end point) (59·1% and 62·6% vs. 29·6%, respectively; P0·001 vs. placebo + TCS, both doses). Other clinical outcomes and atopic dermatitis symptoms were significantly improved in the dupilumab qw + TCS and q2w + TCS groups, including pruritus, pain, sleep disturbance, symptoms of anxiety and depression, and quality of life (QoL). Treatment groups had similar overall rates of adverse events (qw + TCS, q2w + TCS and placebo + TCS groups: 69·1%, 72·0% and 69·4%, respectively) and serious adverse events (1·8%, 1·9% and 1·9%, respectively). Conjunctivitis was more frequent with dupilumab + TCS; skin infections were more frequent with placebo + TCS.Dupilumab + TCS significantly improved signs and symptoms of atopic dermatitis and QoL in adults with a history of inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. No new safety signals were identified.

Summary Background Atopic dermatitis (AD) is a chronic inflammatory skin disease commonly treated with topical corticosteroids. The inflammatory nature of this disorder and the use of topical corticosteroids represent potential risk factors for bone loss. Objectives The aim was to assess the prevalence of osteoporosis and osteopenia in adult patients with moderate to severe AD. In addition, the associations between topical/oral corticosteroid use and bone mineral density (BMD) and between disease activity and BMD were studied. Patients and methods We studied 125 adult patients with moderate to severe AD. Using dual-energy X-ray absorptiometry, BMD was measured at lumbar spine and hips. The cumulative dose of topical and oral corticosteroids was calculated from pharmacy prescription records. Lifestyle parameters were collected by a questionnaire. Biochemical parameters of bone metabolism and disease activity [serum concentration of thymus and activation-regulated chemokine (TARC) levels] were also measured. Results Osteoporosis was documented in six patients (4·8%) and osteopenia in 41 patients (32·8%); 30·4% of the patients had a Z-score ≤ −1 (low BMD), with more men (43·8%) than women (16·4%) affected. There was no significant association between low BMD and biochemical parameters of bone metabolism, serum TARC levels and cumulative dose of topical and oral corticosteroids during the 5 years prior to inclusion. Conclusions We document a Z-score ≤ −1 in about one-third of predominantly male patients with moderate to severe AD, being independent of the cumulative dose of topical and corticosteroids used within 5 years prior to study. Whether the relatively high prevalence of low BMD is due to the cumulative dose of topical corticosteroids beyond 5 years prior to the study or the chronicity of the underlying inflammatory process or a combination of these, remains to be established.

Summary Background Severe atopic dermatitis (AD) is often treated successfully with oral immunosuppressive drugs such as ciclosporin (CsA) or oral corticosteroids. However, some patients develop adverse effects or are unresponsive to these first-choice oral immunosuppressive drugs. Objectives To evaluate whether enteric-coated mycophenolate sodium (EC-MPS) is an effective treatment in patients with severe, recalcitrant AD. Methods Ten patients with severe, recalcitrant AD were treated with EC-MPS 720 mg twice daily for 6 months. All patients had to discontinue other oral immunosuppressive drugs due to adverse effects (n = 8) or nonresponsiveness (n = 2). Disease activity was monitored using the Severity Scoring of Atopic Dermatitis (modified SCORAD) index and the Leicester Sign Score (LSS). Additionally, the level of serum thymus and activation-regulated cytokine (TARC) was measured. During treatment, safety laboratory examination was performed. Total serum immunoglobulin E (IgE) was followed during treatment. Use of topical corticosteroids was recorded before and during treatment. Results Compared with baseline, the mean scores for disease activity significantly decreased during treatment with EC-MPS [modified SCORAD (P = 0·04), LSS severity (P = 0·01), LSS extent (P = 0·01)]. In addition, serum TARC levels and total serum IgE levels significantly decreased after treatment compared with before (P = 0·03; P = 0·05). Disease activity decreased after approximately 2 months of treatment and stabilized during the 6-month treatment period. No differences in the amount of topical corticosteroids used in the 6 months prior to treatment compared with the 6-month treatment period were found (P = 0·4). None of the patients discontinued use of EC-MPS and only mild adverse effects were seen. Conclusions In this study EC-MPS at a dose of 720 mg twice daily for 6 months has proven to be an effective and well-tolerated treatment for patients with severe, recalcitrant AD.

Background Cyclosporin A (CsA) is being increasingly used in the treatment of severe refractory atopic dermatitis. Clinical efficacy and safety of short-term cyclosporin A treatment in atopic dermatitis patients has been proven, however, data on long-term treatment are limited. Objective The aim of this study was to investigate the efficacy, safety and the effect of discontinuation of cyclosporin A treatment in atopic dermatitis patients, with a particular focus on patients treated with cyclosporin A for more than 6 months. Methods We performed a retrospective study of clinical and adverse effects of cyclosporin A treatment in 73 atopic dermatitis patients, with an average duration of cyclosporin A treatment of 1.3 years. Results We included 73 patients (31 women and 42 men, with a mean age of 33.8 years) with severe atopic dermatitis refractory to conventional therapy that was treated with cyclosporin A. Treatment was successful in 56/73 patients. Increases in serum creatinine levels > 30% compared to baseline were reported in 7/73 patients. Arterial hypertension appeared in 11/73 patients during treatment. After discontinuation of treatment, 40/73 patients experienced a relapse and 33/73 patients experienced clinical remission for at least 3 months. No correlation between treatment duration and nephrotoxicity or hypertension was found. Strikingly, 6/73 patients experienced a rebound phenomenon. Conclusions We conclude that CsA is an effective and safe treatment for patients with severe AD refractory to conventional treatment, provided that the recommended guidelines for its administration are strictly observed. However, in contrast to previous reports, we found that 8% (6/73) of patients experienced a rebound phenomenon after discontinuation of treatment.

Contains fulltext : 151851.pdf (Publisher’s version ) (Closed access) BACKGROUND: Long-term data of ciclosporin A (CsA) treatment in daily practice in patients with severe atopic dermatitis (AD) are lacking. OBJECTIVES: To perform a detailed analysis of drug survival, which is the length of time a patient continues to take a drug, for CsA in a long-term daily practice cohort of patients with AD. The secondary objective was to identify determinants of drug survival. METHODS: Data were extracted from a retrospective cohort of patients treated with CsA for AD. Drug survival was analysed using Kaplan-Meier survival curves. Determinants of drug survival were analysed using uni- and multivariate Cox regression analyses with backward selection. RESULTS: In total, 356 adult patients were analysed (386 patient-years). The overall drug survival rates were 34%, 18%, 12% and 4% after 1, 2, 3 and 6 years, respectively. Reasons for discontinuation were controlled AD (26.4%), side-effects (22.2%), ineffectiveness (16.3%), side-effects plus ineffectiveness (6.2%) or other reasons (11.0%). Older age was associated with a decreased drug survival related to controlled AD [hazard ratio (HR) 0.91]. Older age was also associated with a decreased drug survival related to side-effects (HR 1.14). An intermediate-to-high starting dose (> 3.5-5.0 mg kg(-1) daily) was associated with an increased drug survival related to ineffectiveness (HR 0.63). CONCLUSIONS: This is the first study on drug survival for CsA treatment in AD. Older age was associated with decreased drug survival related to controlled AD and side-effects. An intermediate-to-high starting dose was associated with an increased drug survival related to ineffectiveness.

Background: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis patients. We studied the effect of pretreatment with topical tacrolimus 0.1% on APT in nonlesional skin of patients with atopic dermatitis. Methods: Nonlesional skin of the back of patients with atopic dermatitis (n = 8) was treated once daily for 3 weeks with tacrolimus 0.1% ointment. Cetomacrogol ointment (placebo) was used as a negative control and triamcinolone acetonide 0.1% ointment as positive control. Twenty-four hours after the last APT application, samples were taken from the three treated areas (t = 0 and 24 h) for immunohistochemical analysis. Results: Pretreatment with tacrolimus ointment did not suppress nonlesional skin infiltrate, in contrast to triamcinolone acetonide. Furthermore, tacrolimus did not inhibit the induction of the APT macroscopically (t = 24 h). An equal influx of T cells, eosinophils, dendritic cells, CD64+ and FcɛRI-positive cells was present compared with placebo. Only CD36+ and CD68-positive cells were inhibited compared with placebo. All cell types were significantly inhibited in triamcinolone acetonide-treated sites compared with placebo. Conclusions: Pretreatment with tacrolimus 0.1% ointment does not inhibit the APT reaction in patients with atopic dermatitis.